Methods Of New Target Identification

The ideal molecular drug target is one which has been discovered in-house and is proprietary. Alternatively, a receptor or enzyme discovered by a researcher at a university, the cDNA of which is available for licensing by the drug company, could also provide an effective and proprietary target. These targets are often discovered serendip-itously, or could be the result of extensive 'fishing expeditions' using protein biochemistry, immunology (antibody targeting), pharmacology, or molecular biology methods.

Cell and molecular biologists can identify a gene or genes responsible for the cellular variations seen in certain techniques employing subtractive cloning. Total mRNA from normal cells are compared with total mRNA from diseased or modified cells (called normalization). Usually, numerous genes are found to be modified or alternatively expressed, and the mRNA will be detected in the hybridization reactions. The real work comes in sequencing and identifying these genes, and ascertaining which are the unknown, novel sequences. Regarding the newly discovered genes, e.g. potential causes of cell transformation into cancerous tissue, many biochemical and cell biological experiments will be required to determine the function of the protein coded for by the new gene.

Another method of target identification is to raise monoclonal antibodies to cell-surface receptors derived from a cell suspected to be involved in the pathology targeted. Antibodies then identified by FACS (fluorescence activated cell sorting, or labeling techniques) as binding to the target cell are then used in functional assays to prevent a response thought to be critical for disease development. If an antibody can inhibit this response, the antibody is then used by protein biochemists to isolate the culpable receptor.

0 0

Post a comment